tbuckley/cabot-search huggingface dataset:
Increasing the use of olanzapine in patients receiving chemotherapy in a community oncology practice.
Authors: Bindu Rani Potugari, Kathleen W. Beekman, Jane Tolkinen, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2022)

12123 Background: The addition of olanzapine to high emetic risk chemotherapy regimens substantially improves nausea and vomiting within 24 hours and is recommended in the guidelines of both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). However, the uptake of olanzapine has been low in national and institutional settings. The purpose of this project was to increase guideline-concordant prescribing of olanzapine in eligible patients in a community oncology practice. Methods: We developed a multiphase program to address the barriers to the use of olanzapine in a community oncology practice. Patients’ medical records (N = 423) were reviewed to collect baseline data. Motivational interviewing with prescribing clinicians elicited barriers to prescribing, reinforced clinical guidelines, and elicited and reinforced language that suggested a willingness to change prescribing patterns. Chemotherapy protocols were subsequently updated to include olanzapine for high emetic chemotherapy regimens, and prescriber and nurse education was provided by our pharmacists regarding the most recent ASCO and NCCN guidelines. A fellow-led educational session was provided to the infusion nursing team and care managers. At the end of a seven-month period, prescribing information was identified through a system-generated report followed by a medical record review for validation (N = 136) and was shared monthly with prescribing clinicians. Results: At baseline, the use of olanzapine was zero. Multiple barriers were identified regarding the use of olanzapine during motivational interviewing with clinicians, including lack of knowledge of the guidelines, belief that most patients do not require olanzapine, concerns about sedation with the previously recommended dose of 10 mg, and order sets that did not include olanzapine. After the interventions, there was a statistically significant increase in the use of olanzapine from 0% to 56% (p-value &lt; 0.001). Conclusions: A combination of motivational interviewing, prescriber and nurse information support, and changes to the pre-populated order sets for chemotherapy antiemetics was highly successful in improving the uptake of guideline-concordant prescribing of antiemetics. This model of quality improvement, including motivation interview, may support quality improvement efforts across oncology.[Table: see text]
Integrated analysis of genomic alterations of Chinese lung adenocarcinoma with micropapillary component.
Authors: Yongjie Wang, Ronghua Yang, Dong Wang, Shanshan Zhang, Yunpeng Xuan, Peng Li, Lingjie Wang, Shuyu Che, Minghui Han, Yi Yu
Journal: Journal of Clinical Oncology (2022)

e15130 Background: Lung adenocarcinoma (LADC) with micropapillary component (MPC) is a special pathological subtype of LADC, which poses higher invasive with poor prognosis, regardless of proportion of MPC. The effectiveness of molecular targeted therapy in MPC-LADC patients is still being explored without sufficient clinical evidence. Herein, we comprehensive analyzed the genetic alterations of MPC-LADC in order to find effective potential drug-target genes and guide new therapeutic strategies. Methods: We enrolled 31 MPC-LADC patients at Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University from January 2019 to December 2020, and also randomly selected 89 non-MPC-LADC patients as a reference cohort. FFPE or fresh tumors and matched blood samples were performed for NGS-based target panel detection of at least 420 genes (range 420-638 genes), and we analyzed the genomic alterations of the genes with intersection in the above panels sequencing. Results: In our MPC-LADC cohort, the proportion of micropapillary component in 31 tumors were: 5 cases with MPC &lt; 5%, 13 cases with MPC 5% - 20%, 10 cases with MPC ≥20% and other 3 cases unclear. The most frequently mutant genes were EGFR (61.3%, 19/31), TP53 (41.9%, 13/31), ALK (19.4%, 6/31), CTNNB1 (16.1%, 5/31), KRAS (12.9%, 4/31) and SMAD4 (12.9%, 4/31). Moreover, 90.3% (28/31) patients harbored genomic alterations in RTK/RAS/MAPK pathway, 54.8% (17/31) in cell-cycle pathway, 38.7% (12/31) in Wnt pathway, and 19.4% (6/31) in PI3K/AKT/mTOR pathway. Notably, the median age of patients with ALK fusions were younger than wild-type patients (53 vs 60 years, p &lt; 0.05). Patients with KRAS mutations had larger tumor sizes than wild-type patients (Median: 3.4 vs 2.2 cm, p &lt; 0.05), and their lesions are more prone to vascular invasion (p &lt; 0.05). Compared with the reference group of non-MPC-LADC patients, three mutant genes were significantly enriched in MPC-LADC group, namely, CTNNB1 (16.1% vs 1.1%, p &lt; 0.01), ALK (16.1% vs 2.2%, p &lt; 0.05) and SMAD4 (12.9% vs 2.2%, p &lt; 0.05). Finally, we obtained the date of micropapillary lung adenocarcinoma in Memorial Sloan-Kettering Cancer Center (MSK) from cBioPortal database, and survival outcome analysis displayed that EGFR mutations were significantly associated with poor overall survival (OS) (p &lt; 0.05). Conclusions: In this study, we comprehensive revealed the genomic alterations of Chinese MPC-LADC patients and their association with clinicopathological characteristic. Several MPC-enriched genes including EGFR, ALK, KRAS, CTNNB1 and SMAD4 were identified which may be potential genetic drivers of micropapillary lung tumors and could help us to reveal distinct therapeutic avenues of MPC-LADC.
Real-world outcomes of biosimilar bevacizumab-awwb versus reference bevacizumab in patients with metastatic colorectal cancer.
Authors: Catherine Pham, Fang Niu, Thomas Delate, Gary L Buchschacher, Yan Li, Ekim Ekinci, Kim Le, Rita L. Hui
Journal: Journal of Clinical Oncology (2022)

3552 Background: Bevacizumab-awwb was the first biosimilar approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer and became available for use in July 2019. Clinical comparative efficacy and safety of bevacizumab-awwb to bevacizumab was established in a single study of adult patients with advanced non-squamous non-small cell lung cancer. Approval based on extrapolation was granted by the FDA for all other indications, including metastatic colorectal cancer (mCRC). The objective of this study was to evaluate the real-world effectiveness and safety outcomes of patients with mCRC initiated on bevacizumab-awwb versus bevacizumab in an integrated healthcare delivery system. Methods: This was an observational cohort study of patients with mCRC in Kaiser Permanente California, Colorado, and Mid-Atlantic States who were initiated on bevacizumab-awwb between July 2019 and March 2020 or reference bevacizumab between July 2015 and June 2018. Patients with history of bevacizumab use in the 6 months prior to the index treatment date were excluded. Patients were followed until 12 months after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a non-inferiority test with lower margin of 10% and Cox proportional-hazards modeling. Secondary outcomes included count of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events. Results: A total of 1,445 patients initiated on either bevacizumab-awwb (n=239) or bevacizumab (n=1,206) were included in the analysis. The mean overall age was 60 ± 13 years and 54% of patients were male. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab, respectively ( p&lt;0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p=0.93). There were no statistically significant differences in secondary outcomes between the 2 study groups (Table). Conclusions: Bevacizumab-awwb is a safe and effective option when compared to the reference bevacizumab in the treatment of mCRC. Future studies should evaluate outcomes after longer follow-up time and in different cancer types. [Table: see text]
The impact of primary palliative care on advance care planning in advanced cancer.
Authors: Michael Cohen, Andrew Althouse, Edward Chu, Judith Resick, Margaret Q. Rosenzweig, Kenneth Smith, Douglas B. White, Yael Schenker
Journal: Journal of Clinical Oncology (2022)

12030 Background: Palliative care specialists are experts in conducting advance care planning (ACP), but are a limited resource. We sought to determine the impact of a nurse-led primary palliative care intervention on ACP completion among patients with advanced cancer. Methods: We performed a secondary analysis of a cluster randomized controlled trial looking at the impact of nurse-based primary palliative care at community cancer centers. In the parent trial, patients with advanced cancer received either monthly primary palliative care visits with trained nurses within their cancer center or usual care. Nurses in the intervention arm received special training in addressing symptom management and ACP. ACP uptake was assessed at enrollment and 3 months later via validated questionnaire in the forms of an end-of-life conversation (EOLC) with one’s oncologist or completion of an advance directive (AD). The present analyses were restricted to patients without ACP at baseline. Multivariable logistic regression tested differences in ACP uptake by treatment arm when adjusting for age, religious importance, education, time with current oncologist, and ECOG. Results: Of 672 patients enrolled, 182/336 in the intervention arm and 196/336 in usual care lacked an EOLC at baseline and completed three-month assessments. Of those, 82/182 (45.1%) in the intervention arm and 29/196 (14.8%) in the usual care arm reported having an EOLC at three months (Table). Similarly, 111/336 in the intervention arm and 105/336 in usual care lacked an AD at baseline and completed the three-month assessments. Of those, 48/111 (43.2%) in the intervention arm and 19/105 (18.1%) in usual care completed an AD over the study period (Table). For both types of ACP, the treatment effect suggested increased uptake of new ACP in the intervention arm after controlling for variables known to be associated with ACP (Table) Conclusions: Nurse-led primary palliative care increased the uptake of ACP among patients with advanced cancer. Training oncology nurses embedded within community cancer centers may represent a feasible mechanism to improve access to primary palliative care and uptake of advance care planning. Clinical trial information: NCT02712229. [Table: see text]
Paeoniflorin, ASK1-TF, and SOCS3 and association with radiation enteritis.
Authors: Mi Yang, Lei Sheng, Wenjing Fei, Liang Hu, Wen-Tao Liu, Jianxin Ma
Journal: Journal of Clinical Oncology (2022)

e15076 Background: Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “inflammation brake”. We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Methods: Laser doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. Results: It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas 6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and vitro. Conclusions: we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.
Efficacy of osimertinib in patients with <i>EGFR </i>mutant lung cancer harboring the uncommon exon 19 deletion, L747_A750&gt;P.
Authors: Michael J Grant, Jacqueline V Aredo, Jacqueline Starrett, Anna Wurtz, Zofia Piotrowska, Andrew Piper-Vallillo, Helena Alexandra Yu, Christina Falcon, Tejas Patil, Christina Nguyen, Charu Aggarwal, Dylan G. Scholes, Fangyong Li, Manali Phadke, Joel W. Neal, Zenta Walther, Katerina A. Politi, Sarah B. Goldberg
Journal: Journal of Clinical Oncology (2022)

e21112 Background: EGFR exon 19 deletions (del19) are largely considered to have uniform sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Approximately 70% of del19 tumors harbor the most common deletion, E756_A750del; however, many “uncommon” variants comprise the remainder of this group. In preclinical studies, the uncommon del19, L747_A750 &gt; P, demonstrates diminished sensitivity to the third generation TKI, osimertinib [. Identifying differences in clinical outcomes with osimertinib treatment could have therapeutic implications for patients (pts) with EGFR del19 non-small cell lung cancer (NSCLC). Methods: We conducted a multi-center retrospective cohort study of pts with metastatic EGFR del19 NSCLC treated with osimertinib. We compared progression free survival (PFS, time from TKI initiation to clinically significant growth of existing lesions or new lesions on imaging or death) and overall survival (OS) of pts with tumors harboring E746_A750del and L747_A750 &gt; P who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L). The Kaplan Meier method and Cox model were used to estimate PFS and OS, and multivariable logistic regression was used to estimate the odds of achieving PFS &gt; 12 months. Multivariable analyses adjusted for baseline covariates- age, sex, race, and smoking. Results: From March 2013 to December 2021, 86 pts with EGFR E746_A750del and 36 with L747_A750 &gt; P were treated with osimertinib. For 1L osimertinib, E746_A750del was associated with significantly prolonged PFS vs. L747_A750 &gt; P (median 21.3 months (95% CI 17.0-31.7) vs. 11.7 months (10.8-29.4)) in the adjusted analysis (hazard ratio [HR] 0.52 [95% CI, 0.28-0.98, p = 0.043]). Pts with the common del19 mutation were more likely to achieve PFS &gt; 12 months with 1L osimertinib than those with the L747_A750 &gt; P mutation (Odds Ratio 4.14 (1.41-12.15), p 0.0097). OS exhibited a similar trend with a median OS that that was not reached (NR) at 40 months of follow-up among those with E746_A750del vs 26 months for L747_A750 &gt; P (adjusted HR 0.52 [95% CI, 0.23-1.19], p = 0.120). For pts treated with ≥2L osimertinib, there was also a trend towards favorable PFS and OS for pts with tumors harboring E746_A750del. Conclusions: The del19 mutation L747_A750 &gt; P is associated with inferior PFS compared to the common E746_A750del mutation in pts treated with 1L osimertinib. Understanding differences in osimertinib efficacy among EGFR del19 subtypes could alter management of these pts in the future.[Table: see text]
Long-term survival in small-cell lung cancer patients: Extension of the SMALLBRAIN study.
Authors: Javier Diaz-Santos, Alexandra Cantero-Gonzalez, Marta Muñoz-Ayllon, Lucia Garrido-Almazan, Vanesa Gutierrez Calderon, Antonio Rueda Dominguez
Journal: Journal of Clinical Oncology (2022)

e20605 Background: Long-term survivors of metastatic Small Cell Lung Carcinoma (SCLC) with overall survival (OS) greater than 12 months are not frequent and have not been deeply studied. Therefore, we conducted the descriptive study SMALLBRAIN to characterize these patients with central nervous system metastases (mCNS), since at least a 20% of SCLC patients has mCNS at the diagnosis. The survival results were reported at the NCCN 2022 Annual Conference, showing no statistically significant survival difference between presenting mCNS at diagnosis or later and no correlation between the mCNS volume and OS. After these results, we have extended our study to metastatic SCLC patients without mCNS to analyze possible differences. Methods: We carried out a systematic search for metastatic SCLC patients with OS &gt; 12 diagnosed and first treatment between January 2016 and April 2020 in our academic medical center in Spain, we excluded those with missing data. The included patients were classified in 3 cohorts: COHORT NA: Stage III at diagnosis with metastatic progression and no mCNS. COHORT NB: Stage IV patients without mCNS. COHORT Y: mCNS during the course of the disease, regardless of onset time. The number of treatment lines received and the survival were analyzed using Kaplan-Meier and multi-variable Cox proportional hazard analysis. Results: A total of 45 patients met study criteria (NA = 5, NB = 11 and Y = 29). The female - male ratio was of 1:3.14 for cohort Y and 1:2.2 for all the patients without mCNS (NA+NB), not statistically significant. The median OS was 24.9 months for cohort NA (range 16 – 64.83), 21.4 months for NB (range 12.30 – 31.83) and 18.6 months for Y (range 12.67 – 60.83), not statistically significant. Only three patients are currently alive, two from cohort NA and one from Y. The median of treatment lines was 3 for all the cohorts with a maximum of 8 for one patient in cohort Y. Best responses were two complete response with later progression in one patient from cohort NA and one from NB. Best response of cohort Y was a partial response. Conclusions: No statistically significant differences were found regarding survival or treatment lines between the population of long-term survivors of metastatic SCLC with and without mCNS. Their infrequency with few living individuals makes their characterization a challenge. These patients are also highly complex, more than 50% received at least 3 lines of treatment. Future research should explore the possibility of extracting long-term SCLC survivors from existing cancer registries of different countries. [Table: see text]
Association of proton pump inhibitor use with survival outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
Authors: BaoQing Chen, Chen Yang, Mihnea-Paul Dragomir, Dongmei Chi, Wenyan Chen, George Calin, Qiaoqiao Li
Journal: Journal of Clinical Oncology (2022)

2613 Background: Proton pump inhibitors (PPIs) were revealed to regulate gut microbiome alterations and further impact the response to immune checkpoint inhibitors (ICIs). Contradictory impacts on survival were observed in ICI-treated patients when concomitantly use PPI or not. We performed this systematic review and meta-analysis to analyze the association of PPI use with survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases and major oncology conferences proceedings were comprehensively searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI use and PPI non-use in ICI-treated cancer patients were included. Data regarding the characteristics, ICI and PPI treatments and survival outcomes for patients were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effect models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among study results. Results: A total of 20 studies were included, comprising 2812 ICI- and PPI-treated patients and 3990 ICI-treated and PPI-free patients. The pooled HR is 1.30 (95% CI, 1.17-1.45; P &lt;.001) for OS and 1.20 (95% CI, 1.08-1.34; P &lt;.001) for PFS, indicating a significant negative association between PPI use and survival of ICI-treated patients. Subgroup meta-analyses by factors including cancer types, ICI types and time window of PPI use, revealed such associations were in patients with non-small cell lung cancer (OS: HR = 1.40, 95% CI = 1.23 to 1.59, P &lt;.001; PFS: HR = 1.27, 95% CI = 1.16 to 1.40, P &lt;.001) or urothelial cancer (OS: HR = 1.50, 95% CI = 1.26 to 1.80, P &lt;.001; PFS: HR = 1.37, 95% CI = 1.17 to 1.60, P &lt;.001), patients treated with anti-PD-1/PD-L1 (OS: HR = 1.41, 95% CI = 1.30 to 1.53, P &lt;.001; PFS: HR = 1.29, 95% CI = 1.20 to 1.38, P &lt;.001), patients receiving PPI as baseline treatment (OS: HR = 1.43, 95% CI = 1.21 to 1.69, P &lt;.001; PFS: HR = 1.29, 95% CI = 1.16 to 1.44, P &lt;.001) or 60 days before ICI treatment initiation (OS: HR = 1.28, 95% CI = 1.11 to 1.48, P &lt;.001; PFS: HR = 1.27, 95% CI = 1.16 to 1.40, P &lt;.001), rather than concomitantly with ICI initiation. Conclusions: PPIs use in patients treated with ICIs is associated with a shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled, and appear to not impact survival if given temporarily after ICIs initiation. These detailed observations could provide basis for clinical guidelines when concomitantly use PPIs and ICIs.
Efficacy and safety of regorafenib alone or in combinations for advanced hepatocellular carcinoma: A multicenter real-world study.
Authors: Haidong Zhu, Xiaoli Zhu, Yusheng Song, Qi Wang, Jianbing Wu, Hao Xu, Gaojun Teng
Journal: Journal of Clinical Oncology (2022)

e16122 Background: The earlier randomized phase III RESORCE trial demonstrated that regorafenib improved overall survival in advanced hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment, with a median survival of 10.6 months and a hazard ratio of 0.63 (95% CI 0.50-0.79, p &lt; 0.0001). Meanwhile, more data were published from retrospective studies evaluating the sequence of single drug sorafenib and regorafenib in advanced HCC patients treated in real-world settings [eg, REFINE study (N = 1000; 100 from China)].We aimed to explore the efficacy and safety of regorafenib alone or in combinations in advanced HCC patients in a real-world setting. Methods: This retrospective multicenter study included pathologically or clinically diagnosed advanced HCC patients who received regorafenib alone or in combinations in first to fourth line settings for at least 28 consecutive days. The primary endpoints were objective response rate (ORR, RECIST 1.1 criteria) and progression-free survival (PFS). The secondary endpoints included overall survival (OS) rate at 6-month and 12-month, disease control rate (DCR) and safety. Kaplan-Meier method was used to calculate survival data. Results: A total of 61 advanced HCC patients (55 male vs. 6 female, 2 first-line recipients vs. 47 second-line recipients vs.11 third-line recipients vs. 1 fourth-line recipients, median age of 53.5 years) from 6 Chinese centers were included between January 2018 and June 2021. Most patients had BCLC stage C (96.7%) and a Child-Pugh A or B score in 23% or 57.4% of cases respectively. 23 (37.7%) patients received single drug regorafenib therapy, the remaining patients (62.3%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (29.5%), regorafenib combined with TACE (14.8%), and triple therapy (TKI, ICI, TACE) (18.0%). The ORR and DCR of 61 recipients were 71.7% and 83.3%, with a median PFS of 12.67 months (range 7.47-13.97). The 6-month, 12-month OS rates were 80.2% and 68.9%. In second-line recipients, the 6-month, and 12-month OS rates were 85.6% and 76.7%, with a PFS of 12.67 months. 36 recipients had treatment-related adverse events (TRAEs); most frequent TEAEs (≥5%) included fatigue (12.4%), abdominal pain (8.5%), anorexia (7%), rash (7%), diarrhea (6.2%), and hand-foot syndrome (6.2%). Conclusions: Regorafenib alone or in combination is effective and safe in advanced HCC patients, with a high response rate as well as long survival, especially in second-line recipients.